Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• fluorescence response. Compounds that consisted of pyrrole-guanidine attached to larger aryl moieties (pyrene and phenanthridine) bind to the human DPP III enzyme [17]. Pyrene–cyanine conjugates connected with a rigid triazole-peptide linker were designed and synthesized in our group and showed a strong pyrene

• emission change upon binding to proteins, and a cyanine fluorescence that was selective for polynucleotides. Moreover, the FRET pair of chromophores was activated upon binding to biomolecules [18]. Continuing our previous work, two phenanthridine–pyrene conjugates Phen-Py-1 and Phen-Py-2 (Scheme 1

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• with an ionic liquid (EQEmax = 0.12%, Bmax = 10 cd m−2), which was incorporated to increase charge mobility within the emissive layer. We later showed that this emitter could act as host material in combination with a cyanine dye emitter [18]. The EQEmax for this host–guest device was higher than for

• the non-doped device, at 2.0% demonstrated 100% exciton utilization efficiency in the device and efficient energy transfer from the host to the guest cyanine emitter. Deep blue emission in LEECs is challenging. We also reported a blue-emitting LEEC employing a cationic sulfone-based donor–acceptor

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• transform into a green-blue chromophore in the presence of peroxides or redox-active metal ions under acidic conditions, creating a potential detection method for such entities [29]. Additionally, the same structure was used for the preparation of a benzo-1,4-thiazine-based cyanine chromophore, which showed

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• and safe near-infrared (NIR) light is still the subject of intense research efforts but remains a huge challenge due to the associated low photon energy (wavelength from 0.78 to 2.5 µm). In this study, a series of 17 NIR dyes mainly based on a well-established cyanine scaffold is proposed. Remarkably

• , 11 of them were never synthesized before. Markedly, noncharged structures, negatively charged cyanine bearing Na+ as counter cation, and positively charged cyanines bearing (B(Ph)4−) or (I−) as counter anions were examined as promising NIR light photoinitiating systems. Excellent photoinitiating

• polymerization of acrylate/epoxy monomer blends) can also be carried out upon NIR light with the proposed systems. Keywords: cyanine; NIR light; photochemistry; Introduction Photopolymerization processes are well established due to the specific features and advantages. Indeed, the reaction is carried out at

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• delicate balance between the hydrophobic effects of the alkyl chain and the thermodynamically favorable interactions on the association of ammonium or pyridinium groups in the grooves and loops was assessed. In another approach with a cyanine-based ligand, the alkyl substituents with a suitable length were

• with the loops assist the binding to the loops, there is no clear experimental evidence for this binding mode. This observation is in contrast to the report about an arylalkyl-substituted cyanine dye, that has been shown to bind with a high selectivity to particular G4-DNA forms because of additional

• attractive interactions with the loops [49]. In the latter case, however, the quadruplex-binding cyanine unit has been proposed to bind in the groove. In this binding mode, the alkyl-appended aryl functionalities may reach the loops and establish additional binding interactions more efficiently than the

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• -fluorescent at experimental conditions and addition. Since NDI dyes are known to emit fluorescence, we also tried fluorimetric titrations with the hope that the initially non-emissive compound 4 becomes fluorescent upon binding to DNA (for instance cyanine dyes and many other behave that way). However, we did

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• processes requesting heat to initiate either chemical (activated reactions) or physical (melting, evaporation) events. Keywords: chemistry 4.0; cyanine; near infrared; photopolymer; polymer synthesis; sensitizer; Introduction Cyanines have received in the class of polymethines big attention within the

• charge of the final molecule if the cyanine comprises no additional substituent exhibiting a negative charge at the molecular skeleton. Furthermore, it requires to combine this cation with appropriate anions to achieve a good compatibility with the surrounding matrix. Compatibility in these examples

• preferably refers to the solubility in the surrounding matrix, while undesirable events such as aggregation are of minor importance. In the worst case, it can also result in crystallization of the cyanine in the matrix under certain storage conditions such as high humidity and/or elevated temperatures

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• pharmacokinetic or -dynamic properties of the tumor tracers, silicon rhodamines are relatively small and already examined as fluorophores for the optical imaging of tumors. Using silicon rhodamine SiR700 a more enhanced tumor-to-background ratio in optical imaging could be achieved compared to the cyanine based

• could also be successfully applied for optical imaging of a xenograft tumor (human malignant meningioma) in a mouse model [24]. Again, in direct comparison with the cyanine dye Cy5.5, the silicon rhodamine conjugate showed no fading indicating that silicon rhodamine dyes are more suitable for long time

• observation than cyanine-based fluorophores [24]. Different synthetic approaches were established to form the silicon rhodamine framework 1 (Scheme 1). While the group of Wu used a copper(II) bromide-catalyzed solvent-free condensation of a diarylsilane 2 with various benzaldehydes 3 [25], Sparr and Fischer

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• rigid and the molecules can become more or less planar to adopt the constrains of the molecular packing. Thus, the structures of salts 6a and 7a resemble more those of cyanine dyes and the structure of 3 those of merocyanines. The protonation positions of 3 are correctly predicted by the calculations

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• , cyanine and azobenzene have also been reported [18][19][20][21][22][23][24]. High order oligorotaxanes with a multiple number of α- or β-CDs threaded through polymer chains have also been prepared [25][26][27][28]. The interlocked CDs have been shown to provide an interesting insulating effect to π

• [32][33][34][35][36]. By adopting a stepwise stoppering approach, Anderson and co-workers have synthesized a [3]rotaxane consisting of two different axles, derived from a stilbene and a cyanine, threaded through one γ-CD [33]. Inouye has also reported a [3]rotaxane with two pyrene-derived axles

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• challenging tandem hairpin Py/Im polyamides which could recognize >10 base pairs with flexible linker conjugated with a fluorescent dye (either Texas Red (TR) or Cyanine 3 (Cy3)) using a Fmoc-based solid phase synthetic approach; two of the representative conjugates 23 and 24 are shown in the Figure 8 [86][87

• -nucleic-acid-based, sequence-specific DNA-binding molecules. These conjugates could bind to four telomeric repeats with nanomolar dissociation constants, confirmed via SPR analysis. In the similar fashion, Nozeret et al. reported a series of nine fluorescent hairpin polyamides by attaching cyanine and

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• extended backbone at the ligation site [91]. Examples of the fluorogenic templated ligation of PNA are given in Table 1 which include the simple native chemical ligation of two fluorophore-labeled probes [92], formation of cyanine dyes [93][94], fluorogenic Michael addition [95][96] and cross-linking of

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• monomethine cyanine dyes 5a–d, which are analogues of the commercial dsDNA fluorescence binder thiazole orange (TO), have been synthesized. The synthesis was achieved by using a simple, efficient and environmetally benign synthetic procedure to obtain these cationic dyes in good to excellent yields

• fluorescence spectroscopy) and theoretical (DFT and TDDFT calculations) methods. Keywords: cyanine dyes; DFT calculations; green synthesis; nucleic acids; thiazole orange; Introduction Since the discovery by Lee and co-workers [1][2] that the old photographic dye thiazole orange, TO, (Scheme 1) has excellent

• valuable properties as nucleic acid stains have made these dyes an irreplaceable tool in the active and developing area of bioanalytical chemical research [9][10]. Cyanine dyes have found various bioanalytical applications as soluble DNA intercalators (e.g., in living cell imaging [11] and flow cytometry

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• by blue and green emitting cyanine-styryl dyes were improved due to the arabino-configured anchor. These oligonucleotides were used as energy transfer donors in hybrids with oligonucleotides modified with acceptor dyes that emit in the yellow-red range. These combinations give energy transfer pairs

• developed and synthesized the 2’-propargyl-modified arabino-configured uridine analog 2, incorporated it into DNA by automated phosphoramidite chemistry, “clicked” it to a variety of our recently established, photostable cyanine-styryl dyes and probed the fluorescence and energy transfer properties by

• corresponding unmodified counterstrand. The four fluorophores D1 [23], a blue emitter excitable at 389 nm, D2 [24], D3 [19], and D4 [24], all green emitters excitable at 450–460 nm, that were “clicked” to the oligonucleotides DNA1a and DNA1r belong to our recently established class of cyanine-styryl dyes that

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• scattering and absorption by tissue is minimized and a more in-depth therapy becomes possible. The search for more effective compounds with absorption in the near infrared includes amongst others cyanine [10], bodipy [11], and phthalocyanine [12] photosensitizers and has lately led to the consideration of a

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• -NH2 and two fluorophores bearing an azide functional group: one cyanine TO (derivative of thiazole orange [18]), and one coumarine MM14 kindly provided by M. P. Teulade-Fichou (Figure 7). The conjugation was conducted in a microwave reactor as for the polyamide tandem synthesis [2]. The details of the

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• , the use of fluorescent probes requires the covalent binding of large dye molecules (bodipy, cyanine, rhodamine etc, ...) to the drug conjugate, thus potentially modifying its physicochemical profile as well as the in vivo fate and the pharmacological activity. A simple encapsulation of an amphiphilic

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• MRI applications because their Gd(III)-adducts endowed with high relaxivities thanks to much larger molecular masses than the contrast agents themselves. Furthermore, the potential use of cyanine/β-CD carrier systems has been evaluated via in vitro experiments on HeLa cells and the monitoring of cell

• -soluble cyanine/β-CD derivatives have been efficiently prepared via CuAAC under simultaneous US/MW irradiation at 75 °C for 2 h (MW 15 W and US 20 W) in good yields (23% and 33%). These dyes were used as versatile carriers for drug delivery and optical imaging. Preparation of CD-grafted materials and CD

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• these enantiomeric biosensors with orthogonal fluorophores (Figure 5). In our initial experiments, we utilized fluorescein (FAM) and cyanine 3 (Cy3), however, we observed that the difference in fluorophore structure resulted in an approximately two-fold difference in the equilibrium constants for the

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• Emma Werz Helmut Rosemeyer Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastr. 7, 49069 Osnabrück, Germany Ionovation GmbH, Westerbreite 7, 49078 Osnabrück, Germany 10.3762/bjoc.11.103 Abstract A series of six cyanine-5-labeled

• determination of the bilayer brightness using fluorescence microscopy [8]. In the following, we describe the insertion of six unique single-stranded DNA dodecamers carrying different nucleolipid head groups as well as cyanine-5 (Cy5) at the 5’-(n−1) position in artificial lipid bilayers. In this case we varied

• shows the energy-minimized 3D structures of the lipophilic nucleoside headgroups 4a–9a. The reactive building blocks 4b–9b were subsequently used to synthesize the following lipo-oligonucleotides (LONs), which have an identical nucleotide sequence in common as well as a cyanine-5 (Cy5) fluorophore at

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

•  1). Most of the tested ligands, i.e. 1a, 1c, 1d, 2, 4, 5, and 6, induced only a moderate increase of the melting temperature of the ILPR-quadruplex (ΔTm = ca. 2–6 °C). Nevertheless, the addition of the cyanine derivative 1b or the bis-quinolinium derivative 3 induced a significantly larger shift of

• -quinolinium derivative 3 an isosbestic point developed at 364 nm. The addition of ILPR-DNA a2 to the cyanine derivatives 1a–e and 6 resulted in a strong increase of the emission intensity (light-up effect) with increasing concentration of a2 (Figure 5 and Figure 6E). This effect was most pronounced in the

• case of thiazole orange (6) whose emission intensity increases by a factor of I/I0 = 1766. Within the series of heptamethine cyanine dyes 1a–e, the derivative 1d exhibits the largest light-up factor with I/I0 = 128. In contrast, the emission of coralyne (2), bis-quinolinium derivative 3 and the

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• of the phenanthridine/phenanthridinium system for chemical and biochemical research. Widely used fluorimetric dyes, such as cyanine derivatives, are non-fluorescent in the free state but give tremendous fluorescence emission upon binding to biomacromolecular targets. However, many of these dyes show

• non-emissive form in the free state/very strong emission in the bound state, it has several advantages over cyanine dyes: phenanthridine/phenanthridinium fluorescence is characterised by a large Stokes shift (up to 100 nm) allowing the full use of absorption maxima as well as easy incorporation in